The purpose of this proposal is to define an educational proram including course work in toxicology/cell physiology, specific laboratory techniques, a preliminary research plan to be ongoing during the first two years, a specific advanced research plan during the following three years. Environmental and toxic agents induce a myriad of cellular responses when applied to isolated cells, organ models and whole animal or human subjects. How these agents bring about first biochemical changes, then toxic events and finally cell death is an area of significant importance. Therefore, I have constructed a training experience to meet these needs, namely course work and seminars in environmental toxicology, transport physiology and miscellaneous pertinent areas and training in techniques and approaches to calcium transport under the sponsorship of Glenn Langer, M.D. Professor of Physiology and Medicine whose area of research is calcium homeostasis in cardiac muscle cells and the co-sponsorship of Neil Kaplowitz, M.D. Professor of Medicine, whose rea of research is the regulation of glutathione and thiol-disulfide status. The didactic portion of this project will include such courses as toxicology, macromoleculr structure, enzyme chemistry and transport processes. During Phase 1 I will master laboratory techniques, such as spectrophotometry, liquid-scintillation spectrometry, fluorometry, and high pressure liquid chromatography using the laboratories of both sponsors. Isolation of hepatocytes, monolayer culture, flow cell studies, determination of cytosolic free calcium, calcium compartmentation and measurement of reduced and oxidized glutathione will also be learned. I will begin to apply these to specific questions related to the influence of thiol-disulfide status on regulation of calcium homeostasis. Then in phas 2 I will apply what I have learned to determination of the loci and sequence of perturbations of calcium homeostases with representative toxins and assess protective agents.